In 2021, Renske Hebing received the AII Extension grant, a grant to support postdocs that were unable to finish their research project due to COVID. Recently, the research for which Renske Hebing received the extension grant was published in the Annals of the Rheumatic Diseases (ARD), a leading rheumatology journal from the British Medical Journal (BMJ) and the European Alliance of Associations for Rheumatology (EULAR). From the Amsterdam Institute for Infection and Immunity we offer our congratulations to Renske and team! In honor of this publication, we asked Renske Hebing a few questions about the content of her research and how it was made possible in part by the AII Extension Grant.

The research project of Renske Hebing is titled: Pharmacokinetics of Oral and Subcutaneous Methotrexate in Red and White Blood Cells in Patients with Early Rheumatoid Arthritis – the Methotrexate Monitoring Trial. Or in short, the MeMo study. Renske Hebing’s main goal was to answer the following question with her research: What are the pharmacokinetics of methotrexate polyglutamate (MTX-PG) accumulation in red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) in early rheumatoid arthritis (RA) patients after oral and subcutaneous MTX treatment?

The MeMo study

Before we turn to Renske Hebing's own research project, she first tells us what the current status is in her area of research. “To date, several studies have suggested that intracellular levels of methotrexate polyglutamates (MTX-PGs) in red blood cells (RBCs) are useful in predicting MTX (non-)response in Rheumatoid Arthritis (RA) patients. This means that we can measure active metabolites of methotrexate intracellularly and study the link with disease response. However, it can be hypothesized that measurement of MTX-PG levels in the primary immune target cells might improve the predictive value of MTX-PG measurement. Since the primary immune cells are actually involved in the pathway of RA, drug levels in those cells might be more related to the disease status itself.”

Renske wanted to go a step deeper with her research, she says: “The current study expanded our insight in the accumulation of MTX-PG-levels not only in RBCs, but also more importantly in peripheral blood mononuclear cells (PBMCs) as primary target cells. Over 6 months MTX treatment, PBMCs accumulate up to 20-fold higher MTX-PG levels than RBCs. RBCs and PBMCs differ in MTX-PG distribution profiles; remaining fairly constant in PBMCs, while increasing over time in RBCs. Furthermore, subcutaneous MTX administration results in higher drug levels in RBCs (but not in PBMCs) than after oral administration, though only until approximately 3 months after treatment initiation. So it seems that, based on the achieved drug levels, there is no difference. Therefore, the choice of administration route can be based on other characteristics, and is up to the patient and physician, in shared decision”.

The combined MTX-PG analyses in PBMCs and RBCs of Renske’s research team reveals new insights in the pharmacokinetics of MTX accumulation in PBMCs compared to RBCs that may be exploited in future therapeutic drug monitoring studies. For instance, it is now known that early measurement might be more beneficial, already after 1 month, and we are able to see substantial interindividual differences, in PBMCs and RBCs. Furthermore, MTX-PGs in PBMCs might also be useful to estimate therapy adherence.

The AII extension grant

“The AII Extension Grant helped me tremendously.
It helped me (and my colleagues) complete several important analyses. Moreover, it
gave me time to combine my research with my work in the Reade pharmacy.”
Renske Hebing

In 2021, Renske Hebing received the AII Extension grant, a grant to support postdocs who could not finish their research project due to COVID. When we ask Renske to what extent this grant helped her, she is very clear: "This grant helped me tremendously! It helped me (and my colleagues) complete several important analyses. For instance, we have developed a pharmacokinetic/pharmacodynamic model with the MeMo data amongst others, with which we could determine optimal MTX-PG levels in RBCs. And of course it helped us to improve the manuscript itself, to make it suitable for the ARD. Moreover, it gave me time to combine my research with my work in the pharmacy of Reade."

Defense and diapers

The end is in sight: around September Renske's defense will take place and the hard work will be over. Currently, the thesis is being judged by the reading committee and the conversations with a designer and printer are up and running. In the meantime, Renske will enjoy parental leave with her baby, 2-year old son and husband.

Get to know Renske

Renske Hebing is a pharmacist, currently working in the Canisius Wilhelmina Hospital (CWZ) in Nijmegen. Prior to this job, Renske Hebing was working in the research group of Prof. Nurmohamed where she focused on rheumatology from a pharmacotherapeutic perspective. In addition to being work driven, Renske is also sport driven; Renske has been active in middle and long distance running and enjoys driving her racebike. Renske is a warm person: she loves to give advice to people and appreciates honesty and openness. Renske is married and recently she and her husband became parents. Unfortunately, they live a bit further away from Amsterdam these days: in Arnhem, where they renovated a house.

A request from Renske was to end the article with an acknowledgement to her colleagues and patients: “Without my wonderful colleagues, within the pharmacy/Reade/AmsterdamUMC and of course all the patients this unique study wouldn't have been possible. Thank you all very much.”

For more information contact Renske Hebing or read the article here.

Text: Esmée Vesseur